Archive for January, 2009

For decades it didn’t look like clioquinol was going to qualify for the Pharmaceuticals Hall of Fame.

The hydroxyquinoline antibiotic had been used since World War II to treat amoebic infections and shigella gastroenteritis until being blamed for an enormous outbreak of subacute myelo-optic neuropathy in Japan in the 1960s.

There was little scientific reasoning behind the presumed association, and the drug had been used safely by millions before the epidemic but hey, other antibiotics were available to treat the conditions in question so why take a chance?

So the drug passed quietly into retirement, presumably never to be heard from again.

But then out of nowhere, recent animal studies have surfaced purporting to show that clioquinol reverses progression of not one but 3 seemingly unrelated neurodegenerative conditions–Alzheimer’s, Huntington’s and Parkinson’s disease, respectively.

That’s got to be the greatest comeback since Cream rocked Madison Square Garden in 2005.

“The drug affects a gene which when inhibited can slow down aging,” Siegfried Hekimi told the Journal of Life Sciences. “The implication is that we can change the rate of aging. This might be why clioquinol is able to work on this diversity of diseases that are all age-dependent.”

Hekimi and colleagues at McGill University recently reported in the Journal of Biological Chemistry that clioquinol inhibits a mitochondrial enzyme known as CLK-1, or simply “clock-1.”

The mechanism by which clioquinol inhibits CLK-1 remains unclear. “One possibility is that metals are involved as clioquinol is a metal chelator,” Hekimi explained.

Once in awhile, US troops recover an unexploded IED and have look inside. To their dismay, they often find circuit boards, GPS devices and timers produced by US companies.

Iran it turns out, has become adept at acquiring US-made materials that can be used to make IEDs, assembling them and transferring them to a bunch of nut cases in Iraq and Afghanistan.

“The schemes are so elaborate, even the most scrupulous companies can be deceived,” David Albright told the Washington Post. Albright is president of the Institute for Science and International Security and recently co-authored a report on the matter.

And despite one celebrated US government success in interrupting this deadly flow, Iran is still in business.

In 2004, Iranians operating out of 4 Dubai-based front companies including one with the innocuous moniker Mayrow General Trading began scheming to acquire bomb circuitry, according to Justice Department documents.

The companies all used the same managers and business addresses, yet their requisitions appeared legitimate and to be associated with benign projects. The network secured parts from US firms in several states.

In 2006, the Bush administration busted the operation. The Commerce Department subsequently restricted Mayrow’s ability to trade with US companies. Dubai officials helped uncover the operation and have collaborated with US officials ever since.

But months after the bust, the network reconstituted itself in Malaysia under the name Vast Solution. It was a simple matter of changing a few shipping routes and company names. The new enterprise was headed by an Iranian using the name Majid Seif.

In the last few years, the GAO has criticized the FDA for failing to protect our food supply, assure the quality and safety of drugs produced abroad and detect emerging adverse event trends in post-marketing drug surveillance.

So forgive those who barely batted an eye when the GAO called out the agency once again last week, this time for fumbling its fundamental responsibility to assure the safety and efficacy of medical devices.

That pacemaker your Uncle Harry received last week? Almost certainly, it received nothing more than casual look-see from the agency.

The FDA approval process begins by assigning medical devices to one of 3 classes which in turn drives the degree of regulatory scrutiny they recieve.

Reading glasses, tongue depressors and the like are Class I devices, usually exempt from review. Mercury thermometers are Class II, worth at most a quickie.

Class III devices include the good stuff: pacemakers, MRI machines and heart valves for example.

But according to a Congressionally approved 1976 process, Class III products also receive perfunctory reviews if they are found to be essentially similar to devices already on the market.

Or, as Memorial Sloan Kettering physician Peter Bach told the New York Times. “The manufacturer wheels in their new Ferrari and says, ‘Look, it’s just like the Model T,’ ” which is essentially enough to guarantee FDA approval.

“Then they say to doctors, ‘Why would you drive anything but a Ferrari?’ This drives up the cost of care without (necessarily improving) outcomes,” Bach told the New York Times.

In its report, the GAO emphasized “it is imperative that FDA take immediate steps” to put a more rigorous approval process in place for medical devices.

FDA officials insisted to GAO investigators that updating the rules was a priority. But “when asked for their time frame for doing so, the officials did not provide one,” according to the report.

People who get less than 7 hours of sleep per night are 3 times more likely to catch a cold than those who rack up 8 or more, according to a study in the Archives of Internal Medicine.

Sheldon Cohen and colleagues at Carnegie Mellon University recruited 153 healthy adults and paid them $800 if they’d agree to have rhinovirus sprayed up their schnozz and wait to see what happened.

The scientists had obtained detailed sleep histories for each participant before the experiment began.

Five days after the rhino-squirt, immunologic testing revealed evidence of rhinovirus infection in 135 of the participants, yet only 54 developed symptoms of a cold.

The correlation between sleep duration and risk of getting sick was independent of known risk factors such as lack of exercise, stress and smoking.

Cold symptoms are caused by the body’s response to the virus, not the virus itself according to Cohen. People who make just the right amount of anti-virus proteins called cytokines can handle the infection without symptoms.

That’s healthy growth during an economic crisis and newly released premium products by the big dogs, Hershey and Barry Callebaut are largely responsible for driving those numbers, according to the Wall Street Journal.

Even Mars entered the fray, and the world will never be the same thanks to mint chocolate and raspberry almond M&Ms.

Still, when all things economic started getting really nasty in Q4 2008, “growth in the premium chocolate segment slowed,” according to Josiane Kremer, a spokesperson for Barry Callebaut.

So the little guys’ livelihood is threatened, the big dogs’ investors are howling about timing and the resulting competition could scare the clothes off Lady Godiva.

There are consumers who prefer to stick with known brands like Hershey’s but others “want to support small and local producers and that’s where their loyalties are going to lie,” said Krista Faron a senior analyst at Mintel.

And there are consumers who, if chocolate were wine would happily drink Thunderbird. They could care less about cocoa sourcing and the relation between confectionary production methods and product finish.

Or, as Faron summarized, “chocolate may very well be recession-proof — it’s just a matter of how much consumers want to pay for it.”

In letters to thousands of physicians that cared for at least one affected patient, Quest Diagnostics has acknowledged providing incorrect results on Vitamin D tests carried out at its facilities between early 2007 and mid-2008.

Quest is the nation’s largest lab testing company with $7 billion in annual revenue.

Company spokespeople indicated the problem affected less than 10% of all Vitamin D tests done during the period, and that the problem has been resolved. The company is offering free do-overs for affected patients.

Most of the errors involved overstating the true Vitamin D level, which could mean that some patients did not receive supplements as they should have, according to the New York Times.

It’s “the largest patient test recall I’m aware of in my 20 years in the business,” Robert L. Michel told the Times.

Michel edits the Dark Report, a newsletter that broke the story.

The inaccuracies came after Quest shifted to a new Vitamin D assay that relied on mass spectroscopy. The new test had been adopted to improve accuracy and offer more information.

Wael Salameh, a medical director for endocrinology at Quest traced the problem to faulty materials used to calibrate the spectroscopes and to occasional failures to follow proper calibration procedures.

In recent years, Vitamin D testing has surged in response to studies showing that deficiencies of the fat-soluble vitamin are more widespread than had been thought, and are associated with increased risk of bone disease, immune deficiencies, cancer and cardiovascular disease.

Adolescents who act out in class are more likely to experience mental illness, alcohol abuse and both social and financial difficulties later in life, according to a study in the British Medical Journal.

To reach this conclusion, Ian Colman and a team at the University of Alberta queried data involving all 3652 people born in the UK during a one-week period in 1946 using the Medical Research Council National Survey of Health and Development

In this cohort, teachers had documented “externalizing behavior” such as poor attention in class, disobedience, lying, truancy, tardiness, or poor response to discipline when they were 13 and 15 years old.

9.5% of the participants were classified with severe behavioral problems, and another 28.8% with mild problems.

It turned out that those with severe behavioral problems during adolescence were 30% more likely to experience symptoms of anxiety and depression, and twice as likely to experience financial difficulties later in life.

Those with at least mild conduct problems were 40% more likely to abuse alcohol and 2.3 times more likely to be involved with a pregnancy during adolescence.

When it came to dropping out of school, those with mild teen behavioral disturbances were more than twice as likely, and those with severe conduct problems were 4 times more likely.

Divorce was 50% and 70% more likely for those with mild and severe conduct problems in adolescence, and self-reported unhappy family life was 30% and 60% more common in those with mild and severe problems respectively.

The findings held true in men and women and were not affected by educational level.

Pfizer’s $68 billion Wyeth buy must mean the credit spigots have cracked open, deal financing is back and it’s the dawn of the next golden era of M & A, right?

Uh, no. Look at the terms. Pfizer announced it plans to pay for Wyeth using a $22.5 billion loan it negotiated with a 5-bank syndicate, along with equal amounts of stock and cash.

The New York-based drug company, considered to be one of the private sector’s best credit risks and a proud owner of investment-grade credit rating, “agreed to pay 7% to 9% on the loans, which come due in one year,” according to the Wall Street Journal.

Not only that according to WSJ, the syndicate–which includes BoA Merrill Lynch, Barclays, Citigroup, Goldman Sachs and J.P. Morgan Chase can walk if Pfizer’s “credit rating drops below certain thresholds.”

Right on cue, Standard & Poor’s announced it placed Pfizer’s triple-A credit rating on the docket for a downgrade the moment Pfizer announced the deal.

S&P will likely lower Pfizer’s rating to double-A if the deal goes forward due to added leverage and various business challenges faced by the merged entity.

Meanwhile Wyeth’s S&P rating is single-A-plus, just one peg above the minimum required by Pfizer’s deal with the syndicate.

In effect, Wyeth has cast its fate to the ratings agencies. “We realized there’s a new world out there,” a Wyeth insider told WSJ. “You can’t get blood from a stone.”

Amid the unfolding economic crisis, VC investment in clean tech dropped 35% in Q4 2008 when compared to the previous quarter. It was the sharpest fall in 2 years.

A total of $1.7 billion was invested in clean tech during Q4 according to the San Francisco-based market tracking company Cleantech Group.

(Hat tip: Gooz) Clean tech includes solar, clean coal, wind and other technologies that help control industrial pollution and emissions.

Officials at Cleantech Group believe the dropoff is likely to persist through Q1 of this year, but remain optimistic that investment will pick up especially since the Big O indicated he wants to invest heavily in the sector.

“The fundamentals are still strong when it comes to clean tech,” Brian Fan told the Wall Street Journal. Cleantech’s senior director of research added “we know the world has to get off coal and has to replace oil.”

Despite the Q4 downturn, VC investments in the space rose 38% for the year, to an all-time high of $8.4 billion. These numbers have risen every year since 2001 when investments totaled $506.8 million.

There were 241 disclosed investment rounds in the sector in 2008. The most frequent investors were Khosla Ventures (21 separate investments) and Kleiner Perkins Caufield & Byers (18).

Solar power accounted for 40% of the investment in the space, followed by biofuels, transportation and wind.

Many of the larger investments during Q4 2008 were sunk into so-called thin-film solar companies, which produce solar panels from materials other than silicon and are hence notably cheaper.

These days when a deal gets done—and the $68 billion Pfizer-Wyeth tie-up won’t close until Q3 the earliest—it’s so weird people get tongue-tied in their haste to spread the news.

Just 2 weeks ago Pfizer trip-wired news tickers by announcing it would riff 800 researchers, but people knew there had to be more coming if it wanted to retain its title as the biggest fish in the Big Pharma Sea.

Every calendar at Pfizer HQ has 2011—the year Lipitor loses patent protection—circled in red. Lipitor, the best selling drug in the world, accounts for 25% of the company’s $48 billion annual revenue.

Pfizer plans to borrow $22.5 billion from 5 banks to finance its big swallow. It’ll pony up stock and cash to cover the rest. The offer for Wyeth translates to $50 per share, a 29% premium.

Pfizer CEO Jeff Kindler’s legacy will be tied to the Wyeth deal. Since arriving there 2 years ago, he’s fired 15,000 employees, closed labs and sold off production facilities to improve efficiency.

The Wyeth deal affords more such opportunities, but Kindler needs to show more than axe-wielding skills to erase memories of the Exubera fiasco in which the insulin spray was shelved after Pfizer dropped nearly $3 billion on its R & D.

Not to mention that Pfizer had to scrap a heralded Lipitor successor when it was discovered during clinical trials to kill people.

Wyeth’s appeal lies in its pneumoccal vaccine Prevnar, which cleared $2.5 billion in 2008, its anti-inflammatory drug Enbrel and its consumer health business which includes Chapstick, Robitussin and Advil.

Not that all these combined match what Lipitor did for Pfizer, but Kindler had to start somewhere.